Toxoplasma gondii (T. gondii) is a ubiquitous obligate intracellular protozoan parasite that produces opportunistic infections in a large number of warm-blooded animals. This parasite can infect virtually any nucleated animal cell but usually is rapidly controlled by the cellular immune response, leaving only a latent infection that can re-emerge periodically. The asexual reproductive cycle of the parasite is characterized by two stages: rapidly growing tachyzoites and latent bradyzoite tissue cysts. Latent infection with bradyzoites is particularly important for disease propagation and causation.
T. gondii bradyzoites can remain as latent cysts within the tissues of an infected individual for many years. Activation of the interconversion from the bradyzoite to the tachyzoite stage can cause life-threatening opportunistic disease, particularly in immunocompromised individuals, including cancer chemotherapy patients, transplant recipients, and individuals with AIDS or other immunosuppressive disorders. Luft et al., (1988) Clin Infect Dis 15, 211-22); Israelski et al., (1993) Curr Clin Top Infect Dis 13, 322-56. These patients can develop encephalitis or other clinical manifestations due to reactivation of latent cysts, similarly to congenitally infected individuals that mainly develop brain and eye lesions.
In vitro, the induction of bradyzoite-to-tachyzoite interconversion has been associated with changes in temperature, pH, and other stress inducers known to activate expression of heat shock proteins. Morimoto et al., (1994) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Soete et al., (1994) Exp Parasitol 78, 361-370; Tomavo et al., (1991) Infect Immun 59, 3750-3753. Despite its clinical relevance, this conversion has been less thoroughly studied in vivo, although it has been reported that in murine models of chronic infection, subtracting interferon gamma (IFN-γ) induces bradyzoite to tachyzoite interconversion, leading to reactivation of the acute infection. Lyons, et al., (2002) Trends Parasitol 18, 198-201.
There currently exists no effective treatment for chronic toxoplasmosis due to a lack of drugs capable of eliminating tissue cysts.